Summary
This report describes the neuropathological findings in a 32 year old woman with acute myelogenous leukemia (AML) and central nervous system (CNS) involvement, who received a total of 48 mg of methotrexate (MTX) intended to be delivered to the ventricle. At autopsy, the tip of the infusion catheter was found to have been inadvertently placed in the left basal ganglia. The delivery of the MTX at that site caused white matter lesions characteristic of those previously reported in MTX encephalopathy following diverse modes of administration. This case is unusual in that there was the direct infusion of MTX into cerebral parenchyma, circumventing both the blood:brain and cerebrospinal fluid:brain barriers. Axonal abnormalities were widespread in the MTX-infused tissue, frequently but not always accompanied by myelin loss. Since radiation therapy had not been employed, this case permitted the assessment of pathologic changes largely attributable to MTX.
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Balis FM, Poplack DG: Central nervous system pharmacology of antileukemic drugs. Am J Pediatr Hematol Oncol 11: 74–86, 1989
Wilson CB, Norrell HA: Brain tumor chemotherapy with intrathecal methotrexate. Cancer 23: 1038–1045, 1969
Bresnan MJ, Gilles FH, Lorenzo AV, Watters GV, Barlow CF: Leukoencephalopathy following combined irradiation and intraventricular instillation of methotrexate therapy of brain tumors in childhood. Trans Am Neurol 97: 204–206, 1972
Norrell H, Wilson CB, Slagel DE, Clark DB: Leukoencephalopathy following the administration of methotrexate into the cerebrospinal fluid in the treatment of primary brain tumors. Cancer 33: 923–932, 1974
Weiss SR, Raskind R: Brain tumor chemotherapy with intrathecal methotrexate. Cancer 23: 1038–1045, 1969
Breuer AC, Blank NK, Schoene WC: Multifocal pontine lesions in cancer patients treated with chemotherapy and central nervous system radiotherapy. Cancer 41: 2112–2120, 1978
Lee Y-Y, Nauert C, Glass JP: Treatment-related white matter changes in cancer patients. Cancer 57: 1473–1482, 1986
Cohen IJ, Vogel R, Matz S et al.: Successful non-neurotoxic therapy (without radiation) of a multifocal primary brain lymphoma with a methotrexate, vincristine, and BCNU protocol (DEMOB). Cancer 57: 6–11, 1986
DeAngelis LM, Yahalom J, Heinemann MH, Cirrincione C, Thaler HT, Krol G: Primary CNS lymphoma: combined treatment with chemotherapy and radiotherapy. Neurology 40: 80–86, 1990
Stewart DJ: The role of chemotherapy in the treatment of gliomas in adults. Cancer Treat Rev 16: 129–160, 1989
Bleyer WA: Central nervous system leukemia. Pediatr Clin North Am 35: 789–814, 1988
Bleyer WA, Drake JC, Chabner BA: Neurotoxicity and elevated cerebrospinal fluid methotrexate concentration in meningeal leukemia. N Engl J Med 289: 770–773, 1973
Shapiro WR, Chernik NL, Posner JB: Necrotizing encephalopathy following intraventricular instillation of methotrexate. Arch Neurol 28: 96–102, 1973
Rubinstein LS, Herman MM, Long TF, Wilbur JR: Disseminated necrotizing leukoencephalopathy: A complication of treated central nervous system leukemia and lymphoma. Cancer 35: 291–305, 1975
Grossman SA, Trump DL, Chen DCP, Thompson G, Camargo EE: Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. Am J Med 73: 641–647, 1982
Shibutani M, Okeda R: Experimental study on subacute neurotoxicity of methotrexate in cats. Acta Neuropathol 78: 291–300, 1989
Weiss SR, Raskind R: Pathological findings in brain tumors treated with local methotrexate. Int Surg 52: 310–319, 1969
Delattre JY, Rosenblum MK, Thaler HT, Mandell L, Shapiro WR, Posner JB: A model of radiation myelopathy in the rat. Pathology, regional capillary permeability changes and treatment with dexamethasone. Brain 111: 1319–1336, 1988
Price RA, Jamieson PA: The central nervous system in childhood leukemia II. Subacute leukoencephalopathy. Cancer 35: 306–318, 1975
Gilbert MR, Harding BL, Grossman SA: Methotrexate neurotoxicity: in vitro studies using cerebellar explants from rats. Cancer Res 49: 2502–2505, 1989
Flament-Durand J, Ketelbant-Balasse P, Maurus R, Regnier R, Spehl M: Intracerebral calcifications appearing during the course of acute lymphocytic leukemia treated with methotrexate and X-rays. Cancer 35: 319–325, 1975
Shapiro WR, Young DF: Neurological complications of antineoplastic therapy. Acta Neurol Scand Suppl 100: 125–132, 1984
Smith B: Damage to the intrinsic cardiac neurons by rubidomycin (daunorubicin). British Heart Journal 31: 607–609, 1969
Parhad IM, Griffin JW, Clark AW, Koves JF: Doxorubicin intoxication: Neurofilamentous axonal changes with sub-acute neuronal death. J Neurol Exp Neuropathol 43: 188–200, 1984
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Page, K.A., Vogel, H. & Horoupian, D.S. Intracerebral (parenchymal) infusion of methotrexate: report of a case. J Neuro-Oncol 12, 181–186 (1992). https://doi.org/10.1007/BF00172670
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DOI: https://doi.org/10.1007/BF00172670